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The gene editing gold rush continues, and as more than a dozen companies race to develop the first generation of CRISPR gene-editing therapies, newcomer Trucode Gene Repair has a message for investors: There’s more than one way to edit a genome.

The San Francisco-based startup, which was quietly founded in 2017, recently emerged from stealth mode with $34 million from the Silicon Valley venture capital firms Kleiner Perkins and GV (formerly Google Ventures). Trucode is using that cash to develop a new class of gene editing therapies that don’t rely on the bulky enzymes employed by CRISPR-Cas9 gene editing. Instead, the startup is employing synthetic molecules called peptide nucleic acids (PNAs), which impersonate and bind to DNA and can coax the cell’s natural repair machinery into fixing genetic mutations.

In PNAs, the phosphodiester backbone that connects the bases of DNA is replaced with a polyamide backbone, which makes the synthetic strand less susceptible to degradation. Although PNAs were first described in 1991, their potential application in gene editing wasn’t immediately apparent.

In 2002, Yale University geneticist Peter Glazer showed that PNAs could be used to guide a short strand of synthetic DNA to a particular mutation in the genome. Once there, the PNA distorts the cell’s natural DNA, and occasionally prompts the cell to swap the new DNA strand in and throw the mutation-containing segment out. In the nearly two decades since, Glazer and others have tested the ability of new PNA chemistries and designs to make more consistent edits more often.

Glazer, together with Yale colleagues W. Mark Saltzman and Marie E. Egan, developed polymer nanoparticles to deliver gene-editing PNAs in cystic fibrosis mouse models (Nat. Commun. 2015 DOI: 10.1038/ncomms7952). Glazer and Saltzman used the same approach to treat a genetic blood disease called beta-thalassemia in both adult and fetal mice.

These preliminary successes caught the attention of Marshall Fordyce, who led the initial investment and founding of Trucode while he was at Kleiner Perkins and is now Trucode’s CEO. Trucode acquired the rights for PNA-based gene editing from Yale, and also acquired a license from Carnegie Mellon University for its particular flavor of PNA chemistry, in which a polyethylene glycol molecule is attached to a carbon in the polyamide backbone (J. Org. Chem. 2011, DOI: 10.1021/jo200482d). That modification enhances the PNA’s solubility, stability, and ability to fold into a helical structure.

Another company, Pittsburgh-based NeuBase Therapeutics, has also licensed PNA technology from Carnegie Mellon to develop therapies that silence or alter the expression of genes, instead of editing them.

“Gene editing is potentially curative,” Fordyce says, and he’s excited by the potential to use PNAs for many diseases.

Trucode is starting out by focusing on sickle cell disease and cystic fibrosis, but the pipeline posted on its website boasts discovery programs for a dozen diseases including amyotrophic lateral sclerosis, phenylketonuria, and rare genetic diseases of the blood, heart, and liver.

Many of these conditions are the same ones that older CRISPR-based gene-editing companies are already working on. Trucode maintains that it has a potentially attractive alternative.

PNA-based gene editing doesn’t require cutting the DNA, like some forms of CRISPR—although a variant of CRISPR known as base editing can also edit DNA without cutting. Trucode’s system may have the benefit of being smaller and easier to deliver to the body than the bulky enzymes required by CRISPR, but its PNA nanoparticles haven’t been tested in humans, and delivery is never simple for gene editing.